[[2-(Amino-3,4-dioxo-1-cyclobuten-1-yl)amino]alkyl]-acid derivatives for the treatment of pain

A pharmaceutical composition for treating pain comprising:

• a) a pain treating effective amount of at least one compound of formula (I)
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• wherein:
• R1 is hydrogen, alkyl of 1 to 6 carbon atoms or phenylalkyl of 7 to 12 carbon atoms;
• R2 is hydrogen, alkyl of 1 to 6 carbon-atoms, alkenyl of 2 to 6 carbon atoms or phenylalkyl of 7 to 12 carbon atoms;
• or
• R1 and R2 taken together as Z are —CH2CH2—, —CH2C(R6)(R7)CH2— or —CH2C(R8)(R9)—C(R10)(R11)CH2—, where R6, R8 and R10 are, independently, hydrogen, alkyl of 1 to 6 carbon atoms or hydroxyl and R7, R9 and R11 are, independently, hydrogen or alkyl of 1 to 6 carbon atoms;
• A is alkylene of 1 to 6 carbon atoms or alkenylene of 2 to 6 carbon atoms;
• X is CO2R3, P(O)(OR4)(OR5), 3,5-dioxo-1,2,4-oxadiazolidin-2-yl or 5-tetrazolyl wherein R3, R4 and R5 are, independently, hydrogen or alkyl of 1 to 6 carbon atoms;
• or a pharmaceutically acceptable salt thereof;
• and
• b) a pharmaceutically effective amount of at least one pain relieving agent.

A pharmaceutical composition for treating pain comprising:

• a) a pain treating effective amount of at least one compound of formula (I)
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• wherein:
• R1 and R2 taken together as Z are —CH2CH2—, —CH2C(R6)(R7)CH2— or —CH2C(R8)(R9)—C(R10)(R11)CH2—, where R6, R8 and R10 are, independently, hydrogen, alkyl of 1 to 6 carbon atoms or hydroxyl and R7, R9 and R11 are, independently, hydrogen or alkyl of 1 to 6 carbon atoms;
• A is alkylene of 1 to 6 carbon atoms or alkenylene of 2 to 6 carbon atoms;
• X is CO2R3, P(O)(OR4)(OR5), 3,5-dioxo-1,2,4-oxadiazolidin-2-yl or 5-tetrazolyl wherein R3, R4 and R5 are, independently, hydrogen or alkyl of 1 to 6 carbon atoms;
• or a pharmaceutically acceptable salt thereof;
• and
• b) at least one pharmaceutical carrier.

A pharmaceutical composition, in unit dosage form, for treating pain comprising a pain treating effective unit dosage of at least one compound of formula (I)

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• wherein:
• R1 and R2 taken together as Z are —CH2CH2—, —CH2C(R6)(R7)CH2— or —CH2C(R8)(R9)—C(R10)(R11)CH2—, where R6, R8 and R10 are, independently, hydrogen, alkyl of 1 to 6 carbon atoms or hydroxyl and R7, R9 and R11 are, independently, hydrogen or alkyl of 1 to 6 carbon atoms;
• A is alkylene of 1 to 6 carbon atoms or alkenylene of 2 to 6 carbon atoms;
• X is CO2R3, P(O)(OR4)(OR5), 3,5-dioxo-1,2,4-oxadiazolidin-2-yl or 5-tetrazolyl wherein R3, R4 and R5 are, independently, hydrogen or alkyl of 1 to 6 carbon atoms;
• or a pharmaceutically acceptable salt thereof, wherein the composition is in unit dosage form.

A therapeutic package for dispensing to a mammal being treated for pain comprising:

• a) one or more unit dosages of at least one compound of formula (I)
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• wherein:
• R1 and R2 taken together as Z are —CH2CH2—, —CH2C(R6)(R7)CH2— or —CH2C(R8)(R9)—C(R10)(R11)CH2—, where R6, R8 and R10 are, independently, hydrogen, alkyl of 1 to 6 carbon atoms or hydroxyl and R7, R9 and R11 are, independently, hydrogen or alkyl of 1 to 6 carbon atoms;
• A is alkylene of 1 to 6 carbon atoms or alkenylene of 2 to 6 carbon atoms;
• X is CO2R3, P(O)(OR4)(OR5), 3,5-dioxo-1,2,4-oxadiazolidin-2-yl or 5-tetrazolyl wherein R3, R4 and R5 are, independently, hydrogen or alkyl of 1 to 6 carbon atoms;
• or a pharmaceutically acceptable salt thereof;
• and
• b) a container comprising the one or more unit dosages and labeling directing the use of the package for treating pain in a mammal.